HSD11B1 drives colorectal cancer liver colonization through JNK/ HSPB1 axis
Discuss this preprint
Start a discussion What are Sciety discussions?Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
The process of tumor metastasis is multifaceted and intricate. Investigating the mechanistic intricacies that propel the metastatic cascade may unveil novel strategies for interception and targeted therapy. Here, Hydroxysteroid 11-beta dehydrogenase 1 (HSD11B1) is identified as a key mediator in the progression of liver metastases in colorectal cancer, facilitated by drug repurposing and omics analysis. It is found that enhanced expression of HSD11B1 was detected in metastatic tissues, and this upregulation was associated with poor patient survival. Furthermore, overexpression of HSD11B1 was found to facilitate cancer cell invasion and metastasis. Mechanistically, HSD11B1 induces the activation of the MAPK/JNK pathway via phosphorylation, thereby playing a critical role in the liver metastasis of colorectal cancer. Moreover, HSD11B1 interacted with HSPB1, the interaction can be enhanced by JNK MAPK-mediated HSPB1 S78/S82 phosphorylation. Furthermore, pharmacological targeting HSD11B1 by glycyrrhizic acid, suppressing cancer metastasis on CRC mouse models. Overall, these findings unveil a non-canonical function of HSD11B1 in regulating the MAPK/JNK pathway and HSPB1 phosphorylation, positioning HSD11B1 as a potential prognostic biomarker and therapeutic target for CRC with liver metastasis.
